Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleUnusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor.
Publication TypeJournal Article
Year of Publication2013
AuthorsJain, V, Hilton, B, Lin, B, Patnaik, S, Liang, F, Darian, E, Zou, Y, Mackerell, AD, Cho, BP
JournalNucleic Acids Res
Volume41
Issue2
Pagination869-80
Date Published2013 Jan
ISSN1362-4962
Keywords2-Acetylaminofluorene, Aminobiphenyl Compounds, Base Sequence, Circular Dichroism, Deoxyguanosine, DNA Adducts, DNA Damage, DNA Repair, Electrophoretic Mobility Shift Assay, Endodeoxyribonucleases, Escherichia coli, Escherichia coli Proteins, Fluorenes, Models, Molecular, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Nucleic Acid Conformation, Thermodynamics
Abstract

The environmental arylamine mutagens are implicated in the etiology of various sporadic human cancers. Arylamine-modified dG lesions were studied in two fully paired 11-mer duplexes with a -G*CN- sequence context, in which G* is a C8-substituted dG adduct derived from fluorinated analogs of 4-aminobiphenyl (FABP), 2-aminofluorene (FAF) or 2-acetylaminofluorene (FAAF), and N is either dA or dT. The FABP and FAF lesions exist in a simple mixture of 'stacked' (S) and 'B-type' (B) conformers, whereas the N-acetylated FAAF also samples a 'wedge' (W) conformer. FAAF is repaired three to four times more efficiently than FABP and FAF. A simple A- to -T polarity swap in the G*CA/G*CT transition produced a dramatic increase in syn-conformation and resulted in 2- to 3-fold lower nucleotide excision repair (NER) efficiencies in Escherichia coli. These results indicate that lesion-induced DNA bending/thermodynamic destabilization is an important DNA damage recognition factor, more so than the local S/B-conformational heterogeneity that was observed previously for FAF and FAAF in certain sequence contexts. This work represents a novel 3'-next flanking sequence effect as a unique NER factor for bulky arylamine lesions in E. coli.

DOI10.1093/nar/gks1077
Alternate JournalNucleic Acids Res.
PubMed ID23180767
PubMed Central IDPMC3553991
Grant ListP20 RR016457 / RR / NCRR NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States
CA098296 / CA / NCI NIH HHS / United States
CA86927 / CA / NCI NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States